Objective: To develop an evidence-based guideline for the diagnosis and treatment of antipsychotic-induced hyperprolactinemia by adapting existing high-quality clinical guidelines with a view to improve the clinical symptoms and long-term quality of life of patients by providing appropriate management. Methods: This guideline was developed according to the ADAPTE methodology. The adaptation process included determining key health questions, systematically searching and screening guidelines, evaluating the quality and contents of these guidelines, deriving recommendations for key questions, and performing a peer review. The selection criteria for the guideline search were (1) evidence-based guidelines, (2) published within the last 5 years, and (3) written in English or Korean. Results: After evaluating the quality and content, we finally selected three guidelines for adaptation. The final output of the development process was 25 recommendations for 10 key questions. We adopted the Agency for Health Research Quality methodology and presented the level of evidence from levels I to IV. In addition, we defined the recommendation grades from grade A (strongly recommended) to D (no recommendation) based on the level of evidence and clinical significance of the recommendation. Conclusion The development and dissemination of the adapted guideline is expected to increase the certainty of medical decision making and improve the quality of medical care. Further studies on the effectiveness and applicability of the developed guideline are necessary.

Two open-label, randomized, two-period crossover studies were conducted to investigate the pharmacokinetic (PK) properties, safety, and bioequivalence of the test formulation (KD4004), a new fixed-dose combination (FDC) formulation of dapagliflozin and metformin extended release (XR) tablets, relative to the reference formulation (10 mg dapagliflozin/1,000 mg metformin XR FDC tablet) in healthy subjects under fasting (Part A) and fed (Part B) conditions. After giving the dose, serial blood samples were collected for a period of 48 hours. Primary PK parameters (AUC 0-t and C max ) were used to assess bioequivalence between two dapagliflozin/metformin XR (10/1,000 mg) FDC formulations under fed and fasting conditions. Safety and tolerability were also evaluated. Part A and Part B were completed by 32 and 37 subjects, respectively. Bioequivalence of the two FDC formulations of dapagliflozin and metformin XR tablets was established in both the fasted and the fed conditions as the 90% confidence interval of the ratios of adjusted geometric means for AUC 0-t and C max were contained within the predefined range of 0.800–1.250 bioequivalence criteria. Single-dose administration of dapagliflozin and metformin XR was safe and well tolerated as the two FDC formulations. In conclusion, both FDC formulations of dapagliflozin and metformin XR tablets were bioequivalent in fed and fasted subjects. All treatments were well tolerated.

A new fixed-dose combination (FDC) formulation of raloxifene 60 mg and cholecalciferol 800 IU was developed to improve the medication compliance and overall efficacy of raloxifene treatment in postmenopausal osteoporosis patients. The aim of this study was to compare the pharmacokinetics between two tablets of FDC formulation of raloxifene/cholecalciferol and the two products administered concomitantly at respective doses. This randomized, open-label, single-dose, two-treatment, two-way crossover study included 46 volunteers. During each treatment period, subjects received the test formulation (FDC formulation containing raloxifene and cholecalciferol) or the reference formulation (co-administration of raloxifene and cholecalciferol), with a 14-d washout period. Serial blood samples were collected periodically over 96 hours after drug intake. In total, 46 subjects completed the study. The geometric mean ratios and its 90% confidence intervals of the FDC to the single agents for the area under the concentration-time curve from zero to the last quantifiable time point and the maximum plasma concentration met the regulatory criteria for bioequivalence: 1.1364 (1.0584–1.2201) and 1.1010 (0.9945–1.2188) for raloxifene and 1.0266 (0.9591–1.0989) and 1.0354 (0.9816–1.0921) for baseline-corrected cholecalciferol, respectively. Both formulations were well tolerated. No significant differences was observed in the incidence of adverse events between the two treatments. It was concluded that two tablets of the newly developed FDC formulation of raloxifene and cholecalciferol and the corresponding two agents administered concomitantly at respective doses were bioequivalent.

Background: This study was undertaken to compare the sensitivities of mice strains during tumor induction by transcription activator-like effector nucleases (TALEN)-mediated Trp53 mutant gene. Alterations of their tumorigenic phenotypes including survival rate, tumor formation and tumor spectrum, were assessed in FVB/N-Trp53 em2Hwl /Korl and C57BL/6-Trp53 em1Hwl /Korl knockout (KO) mice over 16 weeks. Results: Most of the physiological phenotypes factors were observed to be higher in FVB/N-Trp53 em2Hwl /Korl KO mice than C57BL/6-Trp53 em1Hwl /Korl KO mice, although there were significant differences in the body weight, immune organ weight, number of red blood cells, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count (PLT), total bilirubin (Bil-T) and glucose (Glu) levels in the KO mice relative to the wild type (WT) mice. Furthermore, numerous solid tumors were also observed in various regions of the surface skin of FVB/N-Trp53 em2Hwl /Korl KO mice, but were not detected in C57BL/6-Trp53 em1Hwl /Korl KO mice. The most frequently observed tumor in both the Trp53 KO mice was malignant lymphoma, while soft tissue teratomas and hemangiosarcomas were only detected in the FVB/N-Trp53 em2Hwl /Korl KO mice. Conclusions Our results indicate that the spectrum and incidence of tumors induced by the TALEN-mediated Trp53 mutant gene is greater in FVB/N-Trp53 em2Hwl /Korl KO mice than C57BL/6-Trp53 em1Hwl /Korl KO mice over 16 weeks.

Patients often present with combinations of psychological disorders that manifest with neurological symptoms and/or signs that are not attributable to identifiable structural or functional etiology associated with the nervous system. We present the case of an elderly woman with functional weakness, which was documented using polysomnography with extended surface electromyography. Our findings show that polysomnography with extended surface electromyography may be a useful diagnostic tool for functional weakness in conversion disorder.

Objectives: To investigate whether a history of body injury is associated with obstructive sleep apnea (OSA) in patients with rapid eye movement (REM) sleep behavior disorder (RBD). Methods: We enrolled 56 consecutive patients with RBD, a history of dream-enacting behaviors, and polysomnographic evidence of REM sleep without atonia. Participants were asked whether they had any history of body injuries such as self-injury or bed-partner injury during sleep. The demographic characteristics and polysomnographic parameters of the groups with a history of injury (n=34, 60.7%) and without (n=22, 39.3%) were compared. The association between the history of injury and OSA was assessed. Results: OSA [apnea-hypopnea index (AHI) ≥5/h) was associated with a history of body injury [odds ratio (OR)=6.25, 95% confidence interval (CI)=1.64–23.84]. Additionally, the logistic regression analysis showed that insomnia severity index (OR=0.87, 95% CI=0.80–0.98) and AHI (OR=1.10, 95% CI=1.02–1.18) were associated with history of body injury. Conclusions Therefore, we can conclude that history of body injury is related to obstructive sleep apnea in patients with RBD.

Objectives: Split-night polysomnography (PSG) can be used for the diagnosis and treatment of obstructive sleep apnea (OSA). Recently, the American Academy of Sleep Medicine has broadened the indication of split-night PSG from severe to moderate OSA in a time window of 2 hours. However, majority pieces of evidence have been derived from the male predominant study population. The objective of this study was to investigate the diagnostic accuracy of split-night PSG in Korean women. Methods: This study included 122 adult women with OSA. Apnea-hypopnea index (AHI) from the first 120 minutes of clock time (T120-AHI) and full-night AHI (FN-AHI) were compared using the concordance correlation coefficient (CCC) method and Bland-Altman plot. Receiver operating characteristic (ROC) curves and the area under the ROC curves were plotted with various cut-off points of AHI. Results: The T120-AHI correlated with FN-AHI (CCC=0.77). The area under the ROC curve for T120-AHI with FN-AHI ≥15 was 0.865, with a sensitivity of 78.6% and specificity of 82.7%. Conclusions T120-AHI showed a significant correlation with the FN-AHI value in Korean female patients with OSA.

Dumping syndrome has long been associated with gastric surgery. The authors experienced an adult patient presenting with dumping syndrome after meningitis without any previous surgical procedures on the stomach and small bowel. Dysfunction of the autonomic nervous system after infective meningitis may originate from postinfectious sequelae or an immunologic mechanism. A comprehensive study and proper management of autonomic symptoms of patients with a central nervous system infection are needed.

This study compared the pharmacokinetics of a fixed-dose combination (FDC) of candesartan (16 mg) and amlodipine (10 mg) versus coadministration of individual formulations to clarify the bioequivalence of the FDC. In this randomized, open-label, single-dose, 2-treatment, 2-way crossover study, healthy Korean volunteers received a single dose of candesartan (16 mg) with amlodipine (10 mg) as either an FDC or single agents concomitantly administered, with a 2-week washout period. Serial blood samples were collected up to 72 hours after dosing for each treatment period, and plasma concentrations of candesartan and amlodipine were measured using a validated liquid chromatography-tandem mass spectrometry method. A total of 39 subjects completed the study. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the area under the plasma concentration-time curve from time 0 to the last measurement (AUC0-t) and the peak plasma concentration (Cmax) for candesartan were 1.0182 (0.9562–1.0841) and 0.9492 (0.8726–1.0324), respectively. The GMR and 90% CI for the AUC0-t and Cmax for amlodipine were 1.0552 (1.0255–1.0857) and 1.0668 (1.0259–1.1094), respectively. In conclusion, the new FDC formulation of candesartan (16 mg) and amlodipine (10 mg) was bioequivalent to the concomitant administration of single agents. A single dose of candesartan/amlodipine as the FDC or as single agents was well tolerated.

Patients often present with combinations of psychological disorders that manifest with neurological symptoms and/or signs that are not attributable to identifiable structural or functional etiology associated with the nervous system. We present the case of an elderly woman with functional weakness, which was documented using polysomnography with extended surface electromyography. Our findings show that polysomnography with extended surface electromyography may be a useful diagnostic tool for functional weakness in conversion disorder.